HTLV-I Tax1 and protein kinase C cooperatively activate NF-κB dependent transcription

Paul F. Lindholm*, James Makowski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

HTLV-I is the causal agent of adult T-cell leukemia/lymphoma. Tax1 is the HTLV-I transcriptional activating protein that stimulates virus replication and expression of cell growth genes and cytokines through transcription factors including NF-κB and SRF. Tax1 induced activation and nuclear localization of NF-κB was blocked by calphostin C but not Herbimycin A or H-8. We have previously demonstrated that Tax1 physically associates with and activates PKC. Physical interactions between Tax1 and protein kinase C isoenzymes are compared with Tax1 mutants. In transfection experiments. PKC membrane translocation was analyzed to measure PKC activation in Tax1 expressing Jurkat cells. Transfection with pcTax yielded 59+/-4% of the PKC localized in membrane fractions. In comparison, treatment of Jurkats with the phorbol ester TPA lead to 75% membrane associated PKC while in control cells less than 5% of the PKC was membrane associated. TaxM47 that activates NF-κB and the HIV-1 promoter was associated with 37+/-11% PKC membrane localization. Low levels of membrane associated PKC were detected in Jurkats expressing TaxM22. Cotransfection of Tax1 with PKC a or η isoenzymes lead to a 2 to 3-fold cooperative activation of an NF-κB responsive promoter above Tax1 expression alone. NF-κB DNA binding activity is demonstrated during expression of Tax and PKC isoenzymes. In conclusion, Tax1 and PKC cooperatively activate NF-κB dependent transcription.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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